Accurate behavioral adaptation to stimuli predicting threatening outcome is critical to survival. An insufficient fear reaction may lead the animal to overlook future signs of danger, whereas overreacting may lead the animal to failure to explore and miss opportunities for feeding or mating. A growing body of evidence indicate that the medial prefrontal cortex (mPFC) plays a key role in the control of fear behavior and that distinct prefrontal sub-regions differentially regulate the expression and inhibition of fear responses. Indeed, whereas lesions or inactivations of the mPFC infralimbic (IL) area promote fear expression, the same manipulations applied to the mPFC prelimbic area (PL) promote fear inhibition. Moreover, it has recently been shown that PL and IL receive segregated inputs from anatomically and functionally distinct amygdala neuronal circuits specifically activated during high and low fear states. These data suggest that a key function of mPFC neuronal circuits might be to integrate inputs from the amygdala and other structures involved in fear behavior to ultimately gate fear expression via projections to specific neuronal circuits._x000D_ However, little is known about the underlying PL/IL neuronal circuits. Is the rapid switch between expression/suppression of fear behaviors mediated by the same circuits or does the mPFC contain distinct neuronal circuits dedicated to the control of opposite behaviors? Which synapses are modified during expression/inhibition of fear behavior? Is there an anatomical organization in terms of afferents and efferent at the level of prefrontal single cells or entire circuits? Are there dedicated prefrontal neurons and circuits projecting to specific targets? What could be the role of such circuits for specific aspects of fear behavior? _x000D_ To address these questions we will use an innovative cross-level approach combining in vivo electrophysiological recording techniques, selective optogenetic manipulations and behavioral approaches to elucidate the anatomical and physiological properties of prefrontal excitatory/inhibitory circuits and to address their functional role in the control of fear behavior. In a first step we will examine the activation and connectivity of excitatory and inhibitory PL/IL neuronal circuits controlling fear expression using in vivo single unit extracellular recordings and extracellular stimulations. In a second step, we will selectively manipulate these circuits during behavior using light-activated proteins to test whether the rapid and reversible activation/silencing of neuronal activity causes behavioral alterations. Finally using in vivo intracellular recordings we will study the plasticity and anatomical properties of prefrontal neuronal circuits controlling fear behavior._x000D_ The expected results will provide a detailed knowledge of the cellular basis of fear behavior and of behavioral control in general. Moreover, elucidating the neuronal circuits controlling fear behavior should also lead to novel therapeutic strategies for psychiatric disorders involving dysregulation of emotional responses such as post-traumatic stress disorder and related psychiatric conditions._x000D_